Similar efficacy from specific and non-specific mineralocorticoid receptor antagonist treatment of muscular dystrophy mice
| Autor: | Eric J. Schultz, Jonathan G. Zins, Feni K. Kadakia, Suzanne Smart, Jill A. Rafael-Fortney, Celso E. Gomez-Sanchez, Elise P. Gomez-Sanchez, Jeovanna Lowe, Kyle T. Floyd, Subha V. Raman, Jessica A. Chadwick, Neha Rastogi, Paul M.L. Janssen, Sarah A. Swager |
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| Rok vydání: | 2016 |
| Předmět: |
Male
medicine.medical_specialty Utrophin Duchenne muscular dystrophy Angiotensin-Converting Enzyme Inhibitors 030204 cardiovascular system & hematology Spironolactone Article 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Mineralocorticoid receptor Lisinopril Internal medicine Medicine Animals Muscular dystrophy Muscle Skeletal Mineralocorticoid Receptor Antagonists business.industry Myocardium Antagonist Skeletal muscle Heart Muscular Dystrophy Animal medicine.disease Eplerenone Disease Models Animal medicine.anatomical_structure Endocrinology Treatment Outcome Neurology chemistry Gene Knockdown Techniques Mice Inbred mdx Neurology (clinical) business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Journal of neuromuscular diseases. 3(3) |
| ISSN: | 2214-3599 |
| Popis: | Background: Combined treatment with an angiotensin-converting enzyme inhibitor and a mineralocorticoid receptor (MR) antagonist improved cardiac and skeletal muscle function and pathology in a mouse model of Duchenne muscular dystrophy. MR is present in limb and respiratory skeletal muscles and functions as a steroid hormone receptor. Objective: The goals of the current study were to compare the efficacy of the specific MR antagonist eplerenone with the non-specific MR antagonist spironolactone, both in combination with the angiotensin-converting enzyme inhibitor lisinopril. Methods: Three groups of n = 18 dystrophin-deficient, utrophin-haploinsufficient male mice were given chow containing: lisinopril plus spironolactone, lisinopril plus eplerenone, or no drug, from four to 20 weeks-of-age. Eighteen C57BL/10 male mice were used as wild-type controls. In vivo measurements included cardiac magnetic resonance imaging, conscious electrocardiography, and grip strength. From each mouse in the study, diaphragm, extensor digitorum longus, and cardiac papillary muscle force was measured ex vivo, followed by histological quantification of muscle damage in heart, diaphragm, quadriceps, and abdominal muscles. MR protein levels were also verified in treated muscles. Results: Treatment with specific and non-specific MR antagonists did not result in any adverse effects to dystrophic skeletal muscles or heart. Both treatments resulted in similar functional and pathological improvements across a wide array of parameters. MR protein levels were not reduced by treatment. Conclusions: These data suggest that spironolactone and eplerenone show similar effects in dystrophic mice and support the clinical development of MR antagonists for treating skeletal muscles in Duchenne muscular dystrophy. |
| Databáze: | OpenAIRE |
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